Variant 20-967266-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001029871.4(RSPO4):c.317G>A(p.Arg106Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00731 in 1,614,198 control chromosomes in the GnomAD database, including 208 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.021 ( 93 hom., cov: 33)

Exomes 𝑓: 0.0059 ( 115 hom. )

Consequence

RSPO4
NM_001029871.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.30

Variant links:

Genes affected

RSPO4 (HGNC:16175): (R-spondin 4) This gene encodes a member of the R-spondin family of proteins that share a common domain organization consisting of a signal peptide, cysteine-rich/furin-like domain, thrombospondin domain and a C-terminal basic region. The encoded protein may be involved in activation of Wnt/beta-catenin signaling pathways. Mutations in this gene are associated with anonychia congenital. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Sep 2009]

RSPO4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022935867).

BP6

Variant 20-967266-C-T is Benign according to our data. Variant chr20-967266-C-T is described in ClinVar as [Benign]. Clinvar id is 784403.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RSPO4	NM_001029871.4 linkuse as main transcript	c.317G>A	p.Arg106Gln	missense_variant	3/5	ENST00000217260.9
RSPO4	NM_001040007.3 linkuse as main transcript	c.317G>A	p.Arg106Gln	missense_variant	3/4
RSPO4	XM_017027839.2 linkuse as main transcript	c.317G>A	p.Arg106Gln	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSPO4	ENST00000217260.9 linkuse as main transcript	c.317G>A	p.Arg106Gln	missense_variant	3/5	1	NM_001029871.4	P1	Q2I0M5-1
RSPO4	ENST00000400634.2 linkuse as main transcript	c.317G>A	p.Arg106Gln	missense_variant	3/4	1			Q2I0M5-2

Frequencies

GnomAD3 genomes

AF:

0.0210

AC:

3196

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0631

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.00372

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00376

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.00823

AC:

2054

AN:

249530

Hom.:

AF XY:

0.00742

AC XY:

1005

AN XY:

135390

show subpopulations

Gnomad AFR exome

AF:

0.0613

Gnomad AMR exome

AF:

0.00576

Gnomad ASJ exome

AF:

0.0113

Gnomad EAS exome

AF:

0.00184

Gnomad SAS exome

AF:

0.00510

Gnomad FIN exome

AF:

0.00172

Gnomad NFE exome

AF:

0.00454

Gnomad OTH exome

AF:

0.00858

GnomAD4 exome

AF:

0.00588

AC:

8596

AN:

1461838

Hom.:

115

Cov.:

AF XY:

0.00568

AC XY:

4132

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0656

Gnomad4 AMR exome

AF:

0.00631

Gnomad4 ASJ exome

AF:

0.0118

Gnomad4 EAS exome

AF:

0.000882

Gnomad4 SAS exome

AF:

0.00490

Gnomad4 FIN exome

AF:

0.00195

Gnomad4 NFE exome

AF:

0.00408

Gnomad4 OTH exome

AF:

0.00992

GnomAD4 genome

AF:

0.0210

AC:

3203

AN:

152360

Hom.:

Cov.:

AF XY:

0.0196

AC XY:

1460

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0630

Gnomad4 AMR

AF:

0.0110

Gnomad4 ASJ

AF:

0.0170

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.00375

Gnomad4 OTH

AF:

0.0208

Alfa

AF:

0.00904

Hom.:

Bravo

AF:

0.0233

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.0533

AC:

211

ESP6500EA

AF:

0.00456

AC:

ExAC

AF:

0.00939

AC:

1135

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.00589

EpiControl

AF:

0.00640

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.40

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.26

T;.

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.76

T;D

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.92

L;L

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.096

Sift

Benign

0.10

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.20

B;B

Vest4

0.11

MVP

0.63

MPC

0.070

ClinPred

0.0073

GERP RS

2.0

Varity_R

0.057

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over